Immunogenic cell death in cancer therapy: Present and emerging inducers

Zhou, Jingyi; Wang, Gangyang; Chen, Yinze; Wang, Hongxia; Hua, Yingqi; Cai, Zhengdong

doi:10.1111/jcmm.14356

Cited by 479 publications

(353 citation statements)

References 91 publications

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“…In mesothelioma [188] and multiple myeloma [189], ER-stress-mediated induction of cytotoxic autophagy induces the release of immunogenic signals that make tumors more immunogenic and targetable for the immune system. The induction of immunogenic cell death through ER-stress-mediated autophagy has been described for different drugs, including chemotherapy, being the basis for its combination with immunotherapies such as immune checkpoint inhibitors [190]. Pembrolizumab (anti-PD1) was tested in advanced biliary tract cancer with modest efficacy response rates [191]; therefore, combining ER-stress-mediated inductors of autophagy with chemotherapy to increase tumor immunogenicity and with anti-PD1 treatment could significantly increase the therapeutic ratio.…”

Section: Discussion and Future Perspectivesmentioning

confidence: 99%

Therapeutic Potential of Autophagy Modulation in Cholangiocarcinoma

Pérez‐Montoyo

2020

Cells

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Autophagy is a multistep catabolic process through which misfolded, aggregated or mutated proteins and damaged organelles are internalized in membrane vesicles called autophagosomes and ultimately fused to lysosomes for degradation of sequestered components. The multistep nature of the process offers multiple regulation points prone to be deregulated and cause different human diseases but also offers multiple targetable points for designing therapeutic strategies. Cancer cells have evolved to use autophagy as an adaptive mechanism to survive under extremely stressful conditions within the tumor microenvironment, but also to increase invasiveness and resistance to anticancer drugs such as chemotherapy. This review collects clinical evidence of autophagy deregulation during cholangiocarcinogenesis together with preclinical reports evaluating compounds that modulate autophagy to induce cholangiocarcinoma (CCA) cell death. Altogether, experimental data suggest an impairment of autophagy during initial steps of CCA development and increased expression of autophagy markers on established tumors and in invasive phenotypes. Preclinical efficacy of autophagy modulators promoting CCA cell death, reducing invasiveness capacity and resensitizing CCA cells to chemotherapy open novel therapeutic avenues to design more specific and efficient strategies to treat this aggressive cancer.

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Section: Discussion and Future Perspectivesmentioning

confidence: 99%

Therapeutic Potential of Autophagy Modulation in Cholangiocarcinoma

Pérez‐Montoyo

2020

Cells

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“…ICD is a form of cell death characterized by the chronic release of damage-associated molecular patterns (DAMPs) in the TME [64,68]. Hallmarks of classic ICD include the release of immunomodulatory molecules such as high mobility group box 1 (HMGB1) and adenosine triphosphate (ATP) and surface expression of calreticulin (CR).…”

Section: Hypoxia and Immunogenic Cell Deathmentioning

confidence: 99%

Hypoxia-Driven Immune Escape in the Tumor Microenvironment

Vito

El-Sayes

Mossman

2020

Cells

157

144

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The tumor microenvironment is a complex ecosystem comprised of many different cell types, abnormal vasculature and immunosuppressive cytokines. The irregular growth kinetics with which tumors grow leads to increased oxygen consumption and, in turn, hypoxic conditions. Hypoxia has been associated with poor clinical outcome, increased tumor heterogeneity, emergence of resistant clones and evasion of immune detection. Additionally, hypoxia-driven cell death pathways have traditionally been thought of as tolerogenic processes. However, as researchers working in the field of immunotherapy continue to investigate and unveil new types of immunogenic cell death (ICD), it has become clear that, in some instances, hypoxia may actually induce ICD within a tumor. In this review, we will discuss hypoxia-driven immune escape that drives poor prognostic outcomes, the ability of hypoxia to induce ICD and potential therapeutic targets amongst hypoxia pathways.

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“…In particular, calreticulin exposure stimulates phagocytic activity. HMGB1 is a nuclear protein with adjuvant properties mediated by TLR4 binding, and extracellular ATP secreted during autophagy promotes chemotaxis via P2Y2 receptor [58, 59]. An in vitro study modeling GvHD indicated that pathogenic T cells express calreticulin and release HMGB1 after 8-MOP/UVA exposure, substantially increasing their phagocytosis by DC [60].…”

Section: Platelet Activation and Differentiation Of Monocytes Into DCmentioning

confidence: 99%

Extracorporeal Photopheresis: A Case of Immunotherapy Ahead of Its Time

Vieyra-Garcia¹,

Wolf²

2020

Transfus Med Hemother

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Extracorporeal photopheresis (ECP) is a cell-based immunotherapy that involves the reinfusion of autologous leukocytes after exposure to psoralen and UVA. The treatment has been used for over 30 years, at first on patients with cutaneous T-cell lymphoma (CTCL) and later for the management of patients with graft-versus-host disease (GvHD), sclerosing disorders, atopic dermatitis, and other diseases that may share the common driving factor of a pathogenic T-cell clone or clones in blood circulation. Patients with clinical improvement mount an antigen-specific immune response that may have tolerance traits in the case of GvHD or anticlonal cytotoxic characteristics in the case of CTCL. The exact mechanisms that dictate one response or the other are not fully understood, but the evidence accumulated so far indicates that multiple events occur simultaneously and consequentially contribute to the end result. These include contact of cells with the outside (plastics and tubing of the ECP apparatus), exposure to psoralen and UVA that activates platelets, monocytes, and other myeloid cells, the release of damage-associated molecular patterns, differentiation of monocytes into dendritic cells, and generation and successive presentation of numerous antigens after the phagocytosis of apoptotic cells. Once reintroduced, the ECP product increases the frequency and activity of regulatory T cells (Tregs), shifts the systemic cytokine balance, and promotes extravasation of immune cells that together shape the effects of this treatment. In this review, we summarize the seminal work and most recent literature of the therapeutic mechanisms and reflect on future avenues of improvements and applications of ECP.

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Immunogenic cell death in cancer therapy: Present and emerging inducers

Cited by 479 publications

References 91 publications

Therapeutic Potential of Autophagy Modulation in Cholangiocarcinoma

Therapeutic Potential of Autophagy Modulation in Cholangiocarcinoma

Hypoxia-Driven Immune Escape in the Tumor Microenvironment

Extracorporeal Photopheresis: A Case of Immunotherapy Ahead of Its Time

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